In this program project the core is devoted to improving NMP spectroscopic methods needed in studies proposed by the three other projects on brain, kidney and liver/muscle. The core proposes to improve the necessary NMR localization methods and 1H and 13C spectroscopic methods and to improve the spectrometers performance. It also plans to evaluate the interpretation and quantitation of the NMR results. The brain will use 1H NMR and 1H observed 13C edit methods to measure catabolic fluxes from 1-13C glucose into cerebral pools of glutamate and in some cases lactate. The methods must be improved to obtain maximum sensitivity, resolution and accuracy. The results will then be interpreted quantitatively by evaluating the necessary parameters. In this way the brain project will be helped by the core to study human cerebral metabolism. One of the applications in the brain project of these methods will be to follow the turnover of 13C in lactate pools of stable stroke patients as a guide for therapy. Other directions to be studied in the brain will include time correlations in young adult phenylketonurics between blood and brain levels of phenylalanine. The kidney research will develop methods of quantitating and localizing 1H and 31P NMR spectra of the orthotopic human kidney. Time courses of changes in the osmolytes glycerophosphorocholine and betaine in response to changes in the state of hydration will be followed by 1H and 31P NMR. The NMR resonances will also be used to follow diabetes insipidus, acute renal failure and obstructive nephropathy in humans. 13C NMR measurements of glycogen synthesis and turnover. The roles of insulin/glucose/glucagon in the regulation of liver glycogen gluconeogenesis in humans by using 13C NMR to measure hepatic glycogenolysis in combination with 3 H glucose measurements of whole body glucose turnover rates.